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Volume 59, Issue 3, Pages 343-349 (March 2010)


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The neurosurvival factor Humanin inhibits β-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice

Phuong T. Hoang, Patricia Park, Laura J. Cobb, Valdislava Paharkova-Vatchkova, Michael Hakimi, Pinchas Cohen, Kuk-Wha LeeCorresponding Author Informationemail address

Received 16 June 2009; accepted 3 August 2009. published online 05 October 2009.

Abstract 

Pancreatic β-cell apoptosis is important in the pathogenesis and potential treatment of type 1 diabetes mellitus. We investigated whether Humanin, a recently described survival factor for neurons, could improve the survival of β-cells and delay or treat diabetes in the nonobese diabetic (NOD) model. Humanin reduced apoptosis induced by serum starvation in NIT-1 cells and decreased apoptosis induced by cytokine treatment. Humanin induced signal transducer and activator of transcription 3 and extracellular signal–regulated kinase phosphorylation over a 24-hour time course. Specific inhibition of signal transducer and activator of transcription 3 resulted in nullifying the protective effect of Humanin. Humanin normalized glucose tolerance in NOD mice treated for 6 weeks, and their pancreata revealed decreased lymphocyte infiltration and severity. In addition, Humanin delayed/prevented the onset of diabetes in NOD mice treated for 20 weeks. In summary, Humanin treatment decreases cytokine-induced apoptosis in β-cells in vitro and improved glucose tolerance and onset of diabetes in NOD mice in vivo. This indicates that Humanin may be useful for islet protection and survival in a spectrum of diabetes-related therapeutics.

Division of Pediatric Endocrinology, Mattel Children's Hospital, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA

Corresponding Author InformationCorresponding author. Tel.: +1 310 825 6244; fax: +1 310 206 5843.

PII: S0026-0495(09)00325-4

doi:10.1016/j.metabol.2009.08.001


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